For many years, the unusual bonding, reactivity and planar chirality of trans-cycloalkenes have captured the imagination of scientists. trans-Cyclooctene—the most broadly studied trans-cycloalkene—is resolvable and has a high barrier to racemization (Ea=35.6 kcal/mol). The double bond of trans-cyclooctene is twisted severely in the crown conformation, and as a consequence the HOMO of trans-cyclooctene is high in energy relative to cis-cyclooctene, leading to unusual reactivity. The high reactivity of trans-cyclooctenes has recently produced an impressive resume of applications in synthesis, including reactions with dienes, 1,3-dipoles and ketenes, and strained trans-cyclooctenes can serve as excellent ligands for transition metals. In addition to their usefulness in synthesis, trans-cyclooctenes hold special significance in the field of bioorthogonal chemistry due to their particularly fast kinetics in Diels-Alder reactions with tetrazines. But despite these advances, there remains a need for additional options for conducting bioorthogonal coupling reactions with tetrazines and other compounds.